Improved Sphincter Preservation of Low Rectal Cancer with High Dose Preoperative Radiotherapy: The Lyon R96-02 Randomized Trial

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 21, 2003

Presenter: Jean Pierre Gerard
Presenter's Affiliation: Centre Antoine-Lacassagne, Nice, France
Type of Session: Scientific


    Historically, the management of rectal cancer centered around extensive surgical resection, with local disease control being tantamount and sphincter preservation a low priority. Over the years, with the improvement in radiation therapy techniques and available chemotherapeutic agents, the management of rectal cancer has increasingly shifted towards sphincter preservation. Part of this approach emphasizes the role of preoperative radiation therapy in attempts to downstage patients and permit less extensive surgical resection. Several randomized trials have demonstrated improved sphincter preservation (SP) rates with preoperative compared to postoperative radiation (Lyon R90-01, NSABP R-03). This trial attempted to confirm the SP rates seen in earlier studies, and, more importantly, to further improve upon these rates with higher radiation doses.

Materials and Methods

  • 88 patients enrolled between 1996 and 2001
  • Eligible patients had stage T2-3N0-1M0 rectal adenocarcinoma by endoscopic ultrasound, lesions <6 cm from anal verge, with <2/3 circumferential involvement.
  • Patients randomized to one of two preoperative arms: 1) n= 43 External beam radiation (39 Gy/13 fractions/17 days) 2) n= 45 Same radiation with an endocavitary contact x-ray boost (85 Gy/3 fractions/21 days)
  • Radiation delivered via 3-fields using 18 MV photons and prone patient positioning.
  • Surgery performed 5 weeks later, various approaches depending on patient.
  • Arms well-balanced for age.
  • However, average T size statistically significantly different between arms (arm 1= 3.2 cm vs. arm 2= 2.6 cm, p=0.03).
  • Measured endpoints include SP rates, post-operative morbidity/mortality, local control, and 2-year overall survival.


    Median follow-up = 28 mos Arm 1 vs. Arm 2
  • pT0N0 3 8
  • RT alone, 0 7 Ir-192 boost (25 Gy), no surg
  • Endoanal excision 0 3
  • Anterior resection 19 24
  • Sphincter 19(44%) 3(76%) preservation p=0.004
  • Rates of post-operative deaths, fistulas and other complications were similar in both arms.
  • Overall sphincter quality/function, as measured by MSKCC sphincter function scoring criteria, was comparable in both arms.
  • Two-year survival rates ~90% in both arms.

Author's Conclusions

  • Dose escalation by combining external beam radiation with endocavitary irradiation improves the rates of clinical response, and thus of sphincter preservation, in patients with low-lying rectal adenocarcinomas.
  • This approach does not appear to be associated with increased toxicity over preoperative radiation alone.
  • In order to truly achieve better sphincter preservation rates, surgeons need to adapt their procedures to the patient's disease status following the preoperative treatment. By continuing to perform surgery based on the patient's original stage, the opportunity to downstage and retain the anal sphincter is lost.

Clinical/Scientific Implications

    The results of this study build upon the Lyon group's previous randomized trial (Lyon R90-01) that demonstrated a 40% sphincter preservation rate with the use of preoperative external beam radiation in patients with locally advanced rectal cancer. Delivering higher radiation dose to the tumor with the use of endocavitary contact x-ray treatment, as performed here, increased the sphincter preservation rate to 76%. Furthermore, there was no observed increase in postoperative complications, showing that such dose escalation is both beneficial and plausible. In the US, the boost radiation would likely be delivered using brachytherapy techniques different from the boost in this study. The results of this study support the possibility of another confirmatory trial, this time employing brachytherapy techniques. Additonally, the role of chemotherapy, if any, might be investigated in conjunction with the higher radiation doses to further optimize organ preservation. However, for this, and all similar rectal studies in the future, it is prudent to remember that sphincter preservation is only a desirable endpoint if that sphincter is functional. The importance of assessing patients' quality of life with preserved sphincters can not be overemphasized. It is certainly possible that a subset of patients are actually better served with a more extensive abdominoperineal resection than a lesser surgery that leaves behind a poorly functioning sphincter.

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